The Study to Help the AIDS Research Effort (SHARE) was funded in 1983 by the National Institute of Allergy and Infectious Diseases and the National Cancer Institute. From the beginning, the research in Baltimore was closely coordinated with the clinical sites in Pittsburgh, Chicago and Los Angeles. The resulting collaboration between the four clinical sites, investigators at the NIH and the data center became known as the Multicenter AIDS Cohort Study (MACS). The MACS was designed to be a study of the natural history of risk factors for and progression toward AIDS. Shortly after the study began, HIV (known then as HTLV-III/LAV) was discovered, thus making the study a natural history study of HIV infection. Participants have been seen at least every six months since enrollment began in April 1984. An interviewer-administered questionnaire and a focused physical examination have been performed at each clinical visit. Specimens (including serum, plasma, and cryopreserved peripheral blood mononuclear cells) have been collected at each visit and stored in both national and local repositories. The initial cohort in SHARE consisted of 1,153 gay/bisexual men who were recruited from April to October 1984. Of these, 30% were HIV seropositive at baseline and 104 of the baseline seronegative participants seroconverted. Recruitment was reopened in 1987 in order to recruit partners of current participants and minority gay men. Two hundred forty more participants joined the study, half of whom are African Americans. The prevalence of infection in the newly recruited cohort was 50% at baseline. From the natural history studies in the MACS, we have learned risk factors for infection and the natural history of untreated and treated HIV infection. Immunological, virological, HLA-associated and behavioral factors that may be associated with prolonged or shortened duration of HIV infection are being hotly pursued MACS-wide and in collaboration with investigators from many different institutions. Research into the virological and immunopathological mechanisms of progressive HIV infection are vital areas to be addressed in other applications. This application provides the support for the infrastructure to continue the clinical and epidemiological follow-up of the cohort and to facilitate collaboration with bench scientists both inside and outside of the MACS. A complete description of the clinical spectrum of HIV-associated disorders is also an important area of research for the future. This research will include: epidemiological, nutritional and behavioral factors associated with prolonged survival, and continuing the neuropsychological studies to accurately describe the treated and untreated natural history of these disorders in HIV infection. Therefore, follow-up of cohort members for important post-AIDS outcomes, such as all HIV-related infections, other infections, malignancies, and neuropsychological events and survival is become a primary focus of the study.